In Vitro Mechanistic Studies of a Standardized Sustainable Grape Seed Extract for Potential Application as a Mood-Modulating and Cognition-Enhancing Supplement.

BACKGROUND: Grape seed extract (GSE) from Vitis vinifera L. is rich in polyphenols and oligomeric proanthocyanidin complexes (OPCs), and it has shown potential benefits in managing low mood and cognitive function. In this study, we investigated the potential bioactivities of Enovita(®), a standardized GSE extract (GSEe herein) rich in OPCs, in key mechanistic pathways related to low mood conditions and cognitive function. METHODS: In vitro assays were conducted to assess GSEe's inhibitory effects on γ-aminobutyric acid transaminase (GABA-T) and monoamine oxidase A (MAO-A), its binding affinity to the GABA site of GABA-A receptors, and its effects on acetylcholinesterase (AChE). Its neuroprotective effects on human SH-SY5Y neuroblastoma cells under oxidative stress (induced by H(2)O(2)) were assessed using MTT and LDH release assays. Its antioxidant activities were evaluated using DPPH, ABTS, FRAP, ORAC, HORAC, total phenolic content, and TAS assays. Its cytotoxicity was also evaluated. RESULTS: GSEe showed significant GABA-T inhibitory activity. It also exhibited MAO-A and AChE inhibition, along with moderate binding affinity to the GABA-A receptor. In neuroprotective assays, GSEe provided significant protection to SH-SY5Y cells against oxidative stress. GSEe demonstrated robust antioxidant activity in all assays, including scavenging of DPPH and ABTS radicals, high ferric-reducing power, high polyphenolic contents, and a substantial total antioxidant capacity. CONCLUSIONS: GSEe exhibits promising bioactivities, highlighting its potential as a supplement for modulating mood and enhancing cognitive function. Overall, the promising results from these in vitro studies provide a strong foundation for the continued exploration and development of GSEe as a viable natural supplement for enhancing mental health and cognitive function.